Clinical & Experimental Metastasis

, Volume 30, Issue 4, pp 431–439 | Cite as

Global microRNA profiling in favorable prognosis subgroups of cancer of unknown primary (CUP) demonstrates no significant expression differences with metastases of matched known primary tumors

  • George PentheroudakisEmail author
  • Yael Spector
  • Dimitrios Krikelis
  • Vassiliki Kotoula
  • Eti Meiri
  • Vassiliki Malamou-Mitsi
  • George Fountzilas
  • Mats Sanden
  • Nicholas Pavlidis
  • Hila Benjamin
  • Ranit Aharonov
Research Paper


No data exist on biologic differences between Cancer of unknown primary (CUP) and metastatic solid tumors of known primary site. We assigned a primary tissue of origin in 40 favorable CUP patients (A: serous peritoneal carcinomatosis n = 14, B: axillary adenocarcinoma n = 8, C: upper squamous cervical adenopathy n = 18) by means of a 64-microRNA assay. Subsequently, we profiled the expression of 733 microRNAs (miRs) in the CUP cases and compared results with metastases from 20 ovarian carcinomas, 10 breast adenocarcinomas, 20 squamous head neck or lung tumors. In the Peritoneal CUP versus Ovarian (Known Primary Metastases) KPM comparison, a total of 12 miR were significantly differentially expressed: higher than twofold expression difference in CUP was seen only for miR-513a-5p (3.7-fold upregulated) and miR-483-5p (2.5-fold upregulated), while miR-708 exhibited a twofold downregulation. In the Breast CUP versus Breast KPM comparison, only miR-29c that were downregulated in CUP by 2.7-fold satisfied the FDR threshold. miR-30e and miR-27b, downregulated in ovarian CUPs versus KPMs, were also non-significantly downregulated in breast CUP by 2.0- and 1.4-fold respectively. Six miRs, which belong to the 17–92 oncocluster showed a trend of upregulation in Breast CUP versus Breast KPM cases. A CUP signature remains elusive.


Cancer of unknown primary MicroRNA Gene expression 


Conflicts of interest

George Pentheroudakis, Dimitrios Krikelis, Vassiliki Kotoula, Vassiliki Malamou-Mitsi, George Fountzilas, Nicholas Pavlidis have no conflicts of interest to disclose. Yael Spector, Eti Meiri, Mats Sanden, Hila Benjamin and Ranit Aharonov are employees of Rosetta Genomics. YS, EM, HB and RH hold stock options of the company, which develops miR based diagnostic products and may stand to gain by publications of these findings. Each of the authors is willing to complete an individual, electronic conflict-of-interest form.

Supplementary material

10585_2012_9548_MOESM1_ESM.doc (31 kb)
Supplementary material 1 (DOC 31 kb)


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Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • George Pentheroudakis
    • 1
    Email author
  • Yael Spector
    • 2
  • Dimitrios Krikelis
    • 3
  • Vassiliki Kotoula
    • 4
  • Eti Meiri
    • 2
  • Vassiliki Malamou-Mitsi
    • 5
  • George Fountzilas
    • 3
  • Mats Sanden
    • 6
  • Nicholas Pavlidis
    • 1
  • Hila Benjamin
    • 2
  • Ranit Aharonov
    • 2
  1. 1.Department of Medical OncologyMedical School, University of IoanninaIoanninaGreece
  2. 2.Rosetta Genomics Ltd.RehovotIsrael
  3. 3.Department of Medical OncologyPapageorgiou General Hospital, Medical School, Aristotle University of ThessalonikiThessalonikiGreece
  4. 4.Department of PathologyMedical School, Aristotle University of ThessalonikiThessalonikiGreece
  5. 5.Department of PathologyMedical School, University of IoanninaIoanninaGreece
  6. 6.Rosetta Genomics Inc.PhiladelphiaUSA

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